Abstract
A series of contrast agents for magnetic resonance imaging (MRI) aimed at noninvasively determining the hormone receptor status of cancer in vitro was developed. These MRI contrast agents were prepared by conjugating progesterone to clinically used Gd(III) chelates. These agents exhibited higher progesterone receptor binding affinities in the nanomolar range and intracellular accumulation. High logP values of the modified compounds suggested that the lipophilicity of the steroid conjugates may have contributed to membrane permeability. Synchrotron radiation X-ray fluorescence microscopy and magnetic resonance images revealed that the synthesized conjugates showed the greatest cellular accumulation and significant increase in relaxivity in vitro compared to the previously developed steroid-modified agent. Transcriptional assays using the progesterone response element linked to luciferase indicated that the contrast agents entered the cell, interacted with the biological target, and drove specific progesterone-mediated transcription.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 824-834 |
| Number of pages | 11 |
| Journal | Chemistry and Biology |
| Volume | 14 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 30 2007 |
Funding
We gratefully acknowledge National Institutes of Health grants 1 R01 EB005866-01 (T.J.M.), NIH 5 U54 CA90810 (T.J.M.), and R01 HD044464 (T.K.W.) for support of this work.
Keywords
- CHEMBIOL
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry
